Intermittent treatment with elamipretide preserves exercise tolerance in aged female mice

The pathology of aging impacts multiple organ systems, including the kidney and skeletal and cardiac muscles. Long-term treatment with the mitochondrial-targeted peptide elamipretide has previously been shown to improve in vivo mitochondrial function in aged mice, which is associated with increased fatigue resistance and treadmill performance, improved cardiovascular diastolic function, and glomerular architecture of the kidney. However, elamipretide is a short tetrameric peptide that is not orally bioavailable, limiting its routes of administration. This study tested whether twice weekly intermittent injections of elamipretide could recapitulate the same functional improvements as continuous long-term infusion. We found that intermittent treatment with elamipretide for 8 months preserved exercise tolerance and left ventricular mass in mice with modest protection of diastolic function and skeletal muscle force production but did not affect kidney function as previously reported using continuous treatment.

Automated summary

The pathology of aging affects multiple organ systems. Previous studies have shown that long-term treatment with elamipretide can improve mitochondrial function in aged mice, resulting in various functional improvements. However, elamipretide is not orally bioavailable, limiting its administration routes. This study investigated whether intermittent injections of elamipretide could achieve similar functional improvements as continuous infusion. The results showed that intermittent treatment preserved exercise tolerance and left ventricular mass, but did not have the same effects on kidney function as continuous treatment.